Martha E. Payne

Hippocampal volume in geriatric depression

BACKGROUND There is a growing literature on the importance of hippocampal volume in geriatric depression. METHODS We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects (N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Dukes Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. RESULTS Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume (p =.014) and left hippocampal volume (p =.073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume (p =.052) and to left hippocampal volume (p =.062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. CONCLUSIONS These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

Dorsolateral prefrontal cortex and anterior cingulate cortex white matter alterations in late-life depression

BACKGROUND The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) are critical for mood regulation. Alterations in the white matter connections of these regions may impair their role in mood regulation and increase the risk of developing depression. This study used diffusion tensor imaging to examine for white matter microstructural abnormalities of these regions and of central white matter structures in late-life depression. METHODS One hundred six elderly depressed subjects and eighty-four elderly nondepressed subjects underwent clinical assessment and diffusion tensor imaging. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in regions of interest placed in the white matter of the DLPFC, ACC, corpus callosum, and internal capsule. Differences between groups were assessed, controlling for age, sex, and total cerebral volume. RESULTS After controlling for covariates, depressed subjects had significantly lower FA values in white matter of the right ACC, bilateral superior frontal gyri, and left middle frontal gyrus. There were no significant differences in ADC values. CONCLUSIONS Lower FA, representing lower tissue organization, is observed in depressed elders in the DLPFC and right ACC. These findings support the hypothesis that altered connectivity between brain regions contributes to the risk of depression.

Clinical Characteristics of Magnetic Resonance Imaging-Defined Subcortical Ischemic Depression

BACKGROUND There is a substantial body of research supporting the vascular depression hypothesis of late-life depression. To update this hypothesis so it incorporates recent research, we propose that the term subcortical ischemic vascular depression may be a more accurate representation of the disease process. We sought to investigate this diagnosis as a construct by examining differences between depressed subjects with and without magnetic resonance imaging defined subcortical ischemic vascular depression. METHODS This case-control study examined 139 depressed elderly subjects. Demographic data, psychiatric, medical, and family history, depressive symptomatology, and functional impairment were compared between groups dichotomized based on neuroimaging findings. RESULTS Seventy-five (54%) of the subjects met neuroimaging criteria for subcortical ischemic vascular depression. Age was most strongly associated with increased prevalence of subcortical ischemic vascular depression. Lassitude and a history of hypertension were also positively associated with the diagnosis; a family history of mental illness and loss of libido were negatively associated with the diagnosis. CONCLUSIONS These data support that subcortical ischemic vascular depression may be a specific syndrome from other types of late-life depression. Further research is needed to further characterize this disorder, particularly in regards to cognitive function and treatment implications.

Classification of White Matter Lesions on Magnetic Resonance Imaging in Elderly Persons

White matter lesions, commonly seen on MRIs of elderly people, are related to various geriatric disorders, including cerebrovascular diseases, cardiovascular diseases, dementia, and psychiatric disorders. Currently, white matter lesions are divided into periventricular white matter lesions and deep white matter lesions. Although the meaning of these terms varies by study and this dichotomization itself is still in debate, a possible dissimilarity in pathogenic mechanisms between periventricular white matter lesions and deep white matter lesions are providing some clues for understanding pathophysiology of many geriatric syndromes associated with white matter lesions. We have reviewed the distinctions between periventricular white matter lesions and deep white matter lesions in terms of etiology, histopathology, functional correlates, and imaging methodologies. We suggest a new subclassification of white matter lesions that might have better etiological and functional relevance than the current simple dichotomization. The new categories are juxtaventricular, periventricular, deep white, and juxtacortical. This new classification scheme might contribute to reducing the heterogeneity of white matter lesion findings in future research.

Cortical White Matter Microstructural Abnormalities in Bipolar Disorder

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm2/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.

Hippocampal Volume and Incident Dementia in Geriatric Depression

The authors investigated the role of baseline hippocampal volume on later clinical emergence of dementia in a group of older, non-demented depressed individuals. Subjects were 115 depressed, non-demented participants in a mental health clinical research center. All subjects were screened for dementia and agreed to have a magnetic resonance imaging (MRI) brain scan at baseline. Subjects were clinically evaluated by geriatric psychiatrists quarterly for up to 5 years and received annual neuropsychological testing. Bivariate analyses examined age, gender, race, educational level, baseline depression severity, age at depression onset, baseline Mini-Mental State Exam (MMSE), left and right hippocampal volume, and total cerebral volume. Age, baseline MMSE, total cerebral volume, and having a small left hippocampal volume were associated with later dementia and were included in subsequent survival analysis. Small left hippocampal volume was significantly associated with later dementia (hazard ratio=2.762). Small left hippocampal size on neuroimaging may be a marker for dementia in depressed patients who have not yet met criteria for a clinical diagnosis of a dementing disorder.

Brain choline in depression: In vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy

1. Seven subjects with depression and matched controls were studied using proton spectroscopy to test the hypothesis that choline will be elevated in depression. 2. The proton spectroscopy was repeated after recovery from depression. 3. The study confirmed a state dependent increase in choline in the brain. 4. This change may be used as an in vivo marker of change in depression.

Development of a semi-automated method for quantification of MRI gray and white matter lesions in geriatric subjects

Brain magnetic resonance imaging (MRI) allows for quantitative assessment of hyperintense foci, which are seen with aging and various diseases. These foci, considered to represent lesions, are important in the study of various psychiatric illnesses, including depression. Few quantitative measures have been developed for such research. The goal of the current study was to develop a reliable and efficient method for quantifying the volumes of gray and white matter lesions in MRI scans of the elderly. Interrater reliability was determined by repeat lesion measures on 16 scans. Semi-automated segmentation was performed that identified potential lesions, and then lesions were manually selected based upon detailed anatomic criteria. The lesion quantification procedure took between 25 and 45 min per scan. Reliability intraclass correlation coefficients (ICCs) were 0.99 for both gray and white matter lesions. Volumetric results were found to be moderately correlated with previous lesion ratings (r-values between 0.37 and 0.62, P<0.0001). Among the 700 scans processed with this method, lesion volumes ranged from 0 to 7.3 ml for gray matter, and from 0.4 to 96.8 ml for white matter. Our method proved to be efficient and reliable for quantifying lesions in MRI scans of the elderly.

Diffusion Tensor Measures of the Corpus Callosum in Adolescents With Adolescent Onset Alcohol Use Disorders

BACKGROUND In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent-onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence or abuse) would have myelination microstructural differences compared to controls. METHODS Adolescent subjects (25 males, 7 females) with an AUD (16.9 +/- 1.2 years), who were recruited from substance abuse treatment programs and had co-morbid mental disorders, and 28 sociodemographically similar healthy controls (17 males, 11 females; 15.9 +/- 1.1 years) underwent a 3.0 T MRI diffusion tensor imaging scan. RESULTS Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum microstructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when compared to female adolescents with AUD. CONCLUSIONS Lower MD and higher FA values in the AUD group suggest pre-morbid vulnerability for accelerated prefrontal and temporo-parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum microstructural injury. Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.

Localization of age-associated white matter hyperintensities in late-life depression

OBJECTIVE Deep white matter hyperintense lesions are associated with advanced age and late-life depression. The authors examined where age-related cerebral lesions occurred in elderly depressed and healthy control subjects. METHODS Eighty-seven depressed subjects and 47 control subjects underwent 1.5 T cranial magnetic resonance imaging (MRI). Utilizing a semiautomated method, a segmented image was created containing only white matter lesions. We created a statistical parametric map (SPM) separately for each subject group that displayed the association between lesions in any voxel and advanced age. RESULTS The SPM analysis in depressed subjects demonstrates a significant association between age and lesions found in bilateral, frontal, and left parietal regions. The analysis in control subjects found significant associations only in bilateral parieto-temporal regions, not frontal regions. CONCLUSIONS This study demonstrates a different pattern of age-related lesion location between depressed and control subjects. It further supports the theory that frontostriatal disconnection contributes to late-life depression.